A short introduction to

pheromones for non-chemists

Reprinted with permission from
Pheromones and Animal Behaviour (2003)
by Tristram Wyatt
2003, 2004 Cambridge University Press
This appendix is a free download available from
www.online.ox.ac.uk/pheromones NOT FOR RESALE
Also available for free download is the introductory chapter,
Animals in a chemical worlddescribed by Peter Mombaerts in
Nature Neuroscience as the best overview of pheromones that I
have ever come across, and worth reading by itself from
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This brief introduction to the chemical structure of pheromones is
largely after Stevens in Howse et al. (1998). Like other organic molecules,
pheromones are based on a chain of carbon and attached hydrogen atoms.
The carbon backbone forms a zigzag because of the tetrahedral arrange-
ment of the four carbon bonds (these angles are important for other charac-
teristics of the molecular shape, see Appendix A2 Isomers).
The hydrogen atoms attached to the carbon backbone lie in two planes,
above and below the paper, (represented here by bonds as solid wedges (the
plane above) and as dashed wedges (the plane below)):
The structure is often simplified to show just the carbon backbone:
When other atoms such as oxygen or nitrogen, or other functional
groups, are added to the chain or substituted for hydrogens or carbons, the
chemical nature of the molecule changes (see Table A1.1 for common func-
tional groups).
The naming of compounds tells the reader the length of the carbon
chain and what and where the important functional groups occur. A com-
mon chemical modification of the alcohol group is the combination with an
organic acid (with loss of a water) to give an ester. The naming of the
Appendix A1
An Introduction to Pheromones
for Non-Chemists
302
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molecule reflects the addition of the acid, often acetic acid, to the original
chain, for example to produce dodecan-1-ol acetate:
The name also indicates the number and position of carbon double bonds
(CPC). The formal name for the pheromone of the pink bollworm
(Pectinophora gossypiella) is (Z,E)-7,11-hexadecandien-1-ol acetate (and the Z,Z
isomer; see Appendix A2) (common name Gossyplure). The dien tells us that
there are two double bonds, the 7,11 that these occur at carbons 7 and 11:
APPENDIX A1: AN PHEROMONE STRUCTURE FOR NON-CHEMISTS 303
Table A1.1. Prefixes and suffixes for common functional groups.
Functional group Formula Prex Sufx
Alcohol -OH Hydroxy- -ol
Aldehyde -CHPO Formyl- -al
Amine -NH
2
Amino- -amine
Carboxylic acid -COOH Carboxy- -oic acid
Ester -COOR R-oxycarbonyl- -R-oate
Ketone CPO Oxo- -one
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From Howse et al. (1998).
Pheromone synthesis is catalysed by enzymes and pheromones are
detected by receptors, both of which are proteins, which recognise their sub-
strates and signal molecules (ligands), respectively, by shape in three dimen-
sions. Molecules with atoms in the same formula can also sometimes be put
together in a number of different structures. Even more subtly, molecules
with the same structure (connections between atoms) can have different
shapes in three dimensions. These different variations are called isomers.
This potential variation in molecular shape, in synthesis and reception,
has been acted on by natural selection so that now these variations in shape
are vitally important to many species for species recognition. Each of
the possible isomer types can be important biologically as in each case the
shape of the molecule is different and it may stimulate a different range of
olfactory receptors (Chapter 9).
There are two main different kinds of isomers: constitutional isomers
have the atoms connected in different ways, whereas stereoisomers have the
same connectivity but differ in the arrangement of atoms in space.
A2.1 Constitutional isomers
A2.1.1 Functional group isomers
From the same molecular formula the atoms can be connected in ways that
produce different functional groups, giving quite different chemical prop-
erties to the molecule. For example, n-butyl alcohol (below left) and ethyl
ether (below right) are both C
4
H
10
O
A2.1.2 Positional isomers
Positional isomers differ, for example, in the position of a functional group
(e.g. 2-heptanone and 3-heptanone) or the position of a double bond
Appendix A2
Isomers and Pheromones
OH
O
304
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(e.g. Z-9-tetradecen-1-ol acetate and Z-11-tetradecen-1-ol acetate, the
pheromone components of the summer fruit tortrix moth, Adoxophyes orana):
A2.2 Stereoisomers
Stereoisomers are compounds with identical formulae and order of connect-
ing the atoms together, but with different spatial orientations of the atoms.
In biological systems, driven by enzymes and receptor proteins sensitive to
the shape of molecules, these differences have profound effects. There are a
several types of stereoisomer. These are described in Sections A2.2.1 and
A2.2.2, and the nomenclature used is shown in Table A2.1.
A2.2.1 Chirality and enantiomers (optical isomers)
Chiral molecules are mirror images of each other and, just like your hands,
cannot be superimposed on each other (chiral comes from the Greek word
cheir, meaning hand). The two mirror images are called enantiomers. The
ability to distinguish between a pair of enantiomers requires a chiral agent;
a glove is a chiral agent that distinguishes right and left hands. Enzymes and
receptors are just such systems in biology. Nature is inherently chiral.
APPENDIX A2: ISOMERS AND PHEROMONES 305
O
O
2-heptanone 3-heptanone
9
11
Table A2.1. Naming of isomers: the meanings of the letters and symbols.
The development of chemical nomenclature has left us with a number of different naming
schemes, including some for the same differences, which can be slightly confusing. In addi-
tion, some molecular formulae allow for many possible isomers to be made from them so that
the range of isomers could include, say, geometrical, positional and optical isomers among
the possible molecules sharing the same molecular formula.
Symbols Synonym Type of isomer
E, Z Geometrical spatial arrangement around
double bond
l, d , Optical isomers (laevo, dextro twist of
polarised light)
S, R Different absolute congurations of
stereocenters (assymetric centres)
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CH
3
CH
3
CH
3
CH
2
H
2
C H
3
C
O
H H
O
Mirror
()-carvone
smell: spearmint caraway
()-carvone
The chirality is a consequence of the tetrahedral geometry of carbon atoms:
if different groups are attached to each of the four bonds of one of the carbon
atoms, the molecule can be made in two different ways (or as two enantiomers,
see diagram below). Such a carbon atom is termed a stereocentre or asymmet-
ric centre (in some books this is called a chiral centre). In this and other dia-
grams, dotted lines cc represent bonds going away from you behind the plane
of the paper, solid, thick lines represent bonds coming out of the page to-
wards you. Lines are bonds in the plane of the paper.

A special property of chiral compounds, which led to the discovery of the

phenomenon, is optical activity. Solutions of pure enantiomers rotate the plane
of polarisation of planepolarised light passing through them: opposite enan-
tiomers rotate it in opposite directions. l-Molecules rotate the plane of polarisa-
tion to the left, and d-molecules rotate it to the right. The abbreviations come
from Latin: l (laevo, for left) and d (dextro, right). l and d are often called and
, respectively.
An example of our sensitivity to enantiomers is ()-carvone: this gives us
the smell of spearmint whereas its mirror image, ()-carvone, is perceived
by us as the very different spicy smell of caraway:
A racemic mixture or racemate is an equal mix of the two enantiomers.
As they cancel each other out optically, such solutions do not rotate the
plane of polarisation of light, so they are optically inactive. Most chemically
synthesised compounds, unless enzymes or other special steps are used in
synthesis or purification, are racemic mixtures.
306 APPENDIX A2: ISOMERS AND PHEROMONES
Symmetric:
mirror plane = plane
of paper
bisecting molecule
Mirror
X
A
C
Y
B
X
Y
C
A
B
A
X
Y
A
Asymmetric: two enantiomers
Symmetry and asymmetry in tetrahedral carbon.
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The l, d naming system is based on the observation of the direction inwhich
polarised light is shifted but does not tell us the actual position of all atoms in
space around a molecule. This is done by the absolute configuration, which
uses a rather complicated set of rules which allow the chemist to describe the
absolute configuration at each of the asymmetric centres as either R (from
rectus right) and S (from sinister left). As the R and S are defined according
to a set of nomenclatural rules, these do not necessarily predict which way the
whole molecule will shift polarised light (l/d). (You will see L and D in some
chemical names: these symbols are used to define the absolute configuration
of a sugar or of an amino acid, based on the absolute configuration of glycer-
aldehyde (Fischer nomenclature). D, L (absolute configuration) should not be
confused with d, l (rotation of the plane of polarization of planepolarized
light). The rules for naming are not important here, but biologically, the dif-
ferences are important (see Howse et al. 1998, p. 152).
An example of stereoselectivity in a mammalian pheromone is dehydro-exo-
-brevicomin, which comes in R, R and S, S forms; only the R, R form is active bi-
ologically and only this form is produced by male mice (Novotny et al. 1995):
A2.2.2 Diastereoisomers
When a molecule has more than one asymmetric centre, a second form of
stereoisomerism is possible, diastereoisomerism. Each of the asymmetric
centres can be in one of the two forms, R and S. If there are two asymmetric
centres there will be 2
2
stereoisomers, that is four. For example, 2,3-octandiol
(a pheromone produced by the grape borer beetle Xylotrichus pyrrhoderus)
occurs in four forms: (2R,3R), (2R,3S), (2S,3S) and (2S,3R):
APPENDIX A2: ISOMERS AND PHEROMONES 307
The four optical isomers of 2, 3-octandiol.
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Some of these molecules represent mirror images of each other, for ex-
ample, (2S,3S) and (2R,3R) and are called enantiomers. Other pairs of iso-
mers, such as (2R,3R) and (2S,3R) are not mirror images and these are called
diastereoisomers, that is, they are stereoisomers that are not enantiomers.
These are common in branched compounds. In the case of the grape borer
beetle, only one of the four isomers is attractive (2S,3S).
If there are three asymmetric centres in the molecule there will be eight
isomers (2
3
), as the number of optical isomers is 2
N
where N is the number of
asymmetric centres.
A2.2.2.1 Geometrical isomers
Geometrical isomers are a particular form of diastereoisomer. Many moth
pheromones have particular hydrogens removed, catalysed by specific
desaturase enzymes, to leave double bonds. The double bond makes the
carbon chain rigid at that point. Because of the angles of the chain, there are
two versions of the molecule depending on whether the remaining chains
are connected to (i.e. spatially arranged around) the double bond on oppo-
site sides (E) or the same side (Z) (from the German Entgegen, opposite, and
Zusammen, together). These two forms are different chemical compounds
with characteristic chemical and physical properties. You will also come
across the older terms trans and cis, often roughly equivalent, though not
strictly so by modern objective naming rules, to E and Z respectively.
308 APPENDIX A2: ISOMERS AND PHEROMONES
(Z,E)-7,11-hexadecandien-1-ol acetate
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A short introduction to pheromones for non-chemists
www.cambridge.org/0521485266
Reprinted with permission from Pheromones and Animal Behaviour (2003)
by Tristram Wyatt 2003, 2004 CUP. See www.cambridge.org/0521485266
References:
Howse, P. E., Stevens, I. D. R. & J ones, O. T . (1998). Insect pheromones
and their use in pest management. London: Chapman and Hall.
Novotny, M. V., Xie, T. M., Harvey, S., Wiesler, D., J emiolo, B. &
Carmack, M. (1995). Stereoselectivity in mammalian chemical
communication male-mouse pheromones. Experientia, 51, 738743.
Reprinted with permission from Pheromones and Animal Behaviour (2003)
by Tristram Wyatt 2003, 2004 CUP. See www.cambridge.org/0521485266


Pheromones and Animal Behaviour
Communication by Smell and Taste
Tristram D. Wyatt
University of Oxford
We are entering one of the most exciting periods in the study of chemical communication
since the first pheromones were identified some 40 years ago. This rapid progress is
reflected in this book, the first to cover the whole animal kingdom at this level for 25 years.
The importance of chemical communication is illustrated with examples from a diverse
range of animals including humans, marine copepods, Drosophila, Caenorhabditis
elegans, moths, snakes, goldfish, elephants and mice. It is designed to be advanced and
up-to-date, but at the same time accessible to readers whatever their scientific
background. For students of ecology, evolution and behaviour, this book gives an
introduction to the rapid progress in our understanding of olfaction at the molecular and
neurological level. In addition, it offers chemists, molecular and neurobiologists an insight
into the ecological, evolutionary and behavioural context of olfactory communication.

Pheromones are by far the most important signals used by organisms of all
kinds. Wyatts book is an excellent text and review: up-to-date,
comprehensive, balanced, detailed, clearly written, and nicely illustrated.
Edward O. Wilson

Contents: 1. Animals in a chemical world; 2. Discovering pheromones; 3. Sex
pheromones: finding and choosing mates; 4. Coming together and keeping apart:
aggregation and host-marking pheromones; 5. Scent marking and territorial behaviour; 6.
Pheromones and social organization; 7. Pheromones and recruitment communication; 8.
Fight-or-flight: alarm pheromones; 9. Perception and action of pheromones: from receptor
molecules to brains and behaviour; 10. Finding the source: pheromones and orientation
behaviour; 11. Breaking the code: illicit signallers and receivers of semiochemical signals;
12. Using pheromones: applications; 13. On the scent of human attraction: human
pheromones?; Appendix A: An introduction to pheromones for non-chemists; References.
2003 246 x 189 mm 408pp 118 line diagrams 28 half-tones 18 tables

For further information, please visit www.cambridge.org/0521485266



More reviews available at www.online.ox.ac.uk/pheromones
Pheromones and Animal Behaviour
Communication by Smell and Taste
Tristram D. Wyatt (2003)
www.cambridge.org/0521485266
Other books of interest at CUP
Advances in Insect Chemical Ecology
Edited by R.T. Card & J .G. Millar (2004)
www.cambridge.org/0521792754
Animal Communication Networks
Edited by P.K. McGregor (2005)
www.cambridge.org/0521823617
Chemical Ecology of Vertebrates
D. Mller-Schwarze (available from J uly 2006)
www.cambridge.org/0521363772